Abstract : Members of the U.S. Armed Forces receive immunization with vaccinia virus vaccine. Efforts to develop a safe and effective tissue culture-derived vaccinia vaccine to replace the standard vaccine produced by scarification on cows' skin have advanced early clinical studies. It is generally accepted that protection induced by the conventional vaccinia vaccine correlated with cellular immune responses to live experimental and standard vaccinia vaccines. During the two years of this contract we have: (1) obtained, separated and cryopreserved peripheral blood mononuclear cells from 92 vaccinees in a clinical study to compare the standard and an experimental small pox vaccine, (2) prepared live and killed vaccinia virus antigens, (3) performed lymphocyte proliferation and cytotoxic T cell assays and (4) performed immunoblot assays on vaccine donor samples. Both vaccines stimulated vaccinia virus-specific humoral and cellular immune responses in the vacinees, however, the standard smallpox vaccine stimulated significantly stronger immune responses through the traditional cutaneous route of inoculation.